Transplants

When I first met Cassie Stockton, she was seated in an exam chair in Stanford’s dermatology clinic, getting cosmetic skin treatments. Lovely and young, just 21 years old, it seemed a bit silly. How could she possibly need injectable lip fillers or laser skin treatments?

I knew Stockton had a lung transplant at 15 and that the immunosuppressant drugs she was required to take to keep her body from rejecting the donated lungs had made her susceptible to skin cancer. But it wasn’t until I researched her story in depth that I truly understood how she ended up needing regular cosmetic treatments here.

As I explain in my recently published Stanford Medicinearticle, her story began at birth:

Born premature, [Cassie] was intubated the first two weeks of life, then sent home with her mother and an oxygen tank. She remained on oxygen 24 hours a day for the first two years of her life. Eventually, she was diagnosed with bronchopulmonary dysplasia, a chronic lung disorder …

Sixteen years later, the donated gift of new lungs saved her life – but it left scars, both emotional and physical:

The day Stockton woke up out of the anesthesia six years ago after a 13-hour surgery at the Transplant Center at Lucile Packard Children’s Hospital Stanford, she breathed in oxygen with newly transplanted lungs, and breathed out sobs. Tears streamed down her face. “At first, I thought she was in pain,” says her mother, Jennifer Scott, who stood by her side. But that wasn’t it. Stockton was overwhelmingly sad because she now knew her new lungs were the gift of a child. It was Dec. 6, 2009, just before Christmas. The death of someone else’s child had given her a whole new life.

And now:

Every four months, she and her fiancé make the four-hour drive from their home in Bakersfield, California, past the oil rigs and cattle farms to Stanford’s Redwood City-based dermatology clinic for her skin cancer screening. It’s been two years of treatments: freezings, laserings, a total of eight outpatient skin surgeries — the most significant resulting in the removal of the left half of her lower lip. The dermatologic surgeon removes the skin cancers, and then gets to work to repair the damage. “It’s heart-breaking to have to remove the lip of a 21-year-old woman,” says Tyler Hollmig, MD, clinical assistant professor of dermatology and director of the Stanford Laser and Aesthetic Dermatology Clinic, who leads Stockton’s treatment and keeps her looking like the young woman she is, restoring her skin, rebuilding her lip, making sure she keeps her smile.

Stockton doesn’t complain about any of the struggles she’s had post transplant. She knows she got a second chance at life. And, she tells me, it’s her job to take care of the lungs given to her by that child who died.

I wrote a press release recently on a study that showed a high percentage of donated hearts were not being used, raising concerns that some were getting wasted when they could be used to save lives. This made me curious about the process of just how a donor heart, which ideally has about a two-hour window before it gets transplanted to a patient with heart failure, gets matched.

The result is a Stanford Medicine magazine story titled “Heart Choices” that describes this process, the tough decisions that family members make when a loved one donates a heart, and the excruciating waiting that patients in need of a new heart go through.

Most importantly the article asks the question: Should more “high-risk” donor hearts be used? An estimated 20,000 people across the country are waiting for new hearts, and only a few thousand transplants happen on average per year. My story explains the dilemma:

The general assumption is that there simply are not enough donor hearts available to meet a growing demand. But new research is questioning that assumption. Some researchers and surgeons claim that thousands of donor hearts that could be used are turned away each year. The hearts are considered marginal because they come from older, sicker or riskier donors, but many argue they are safe for transplant, and could be saving lives.

“As patients wait longer, they often get sicker, and we often lose patients,” says Stanford cardiologist Kiran Khush, MD, whose research reports that 65 percent of available heart donations are discarded because of stringent acceptance criteria. Yet the criteria have not been critically evaluated, she says. “Increasing the supply of donor hearts is, of course, a great concern of mine.”

Much of medical science writing involves reporting on the next potentially lifesaving treatment. But sometimes it’s rewarding to look back. The recent death of one of Stanford’s first kidney donors had me doing just that – and exploring a time when this now-common procedure was cutting edge.

Inga Goodnight, who died at the age of 99 in April, donated her kidney to her son Gary, who went on to live another 37 years.

Today, kidney transplants are established procedures; more than 17,000 were performed in the United States last year. Improvements in surgery and immunosuppressive drugs have increased the number of potential kidney matches. Studies have shown that donors have no increased health risks compared with the general public.

But in 1965, when Gary became the third patient to receive a kidney transplant at Stanford, many things were unknown. Doctors were still determining proper dosages for the immunosuppressive drugs, and they didn’t know if Gary’s body would reject the kidney or if he would even survive the first year.

While it was known that a person could live with one kidney, no one knew if there would be long-term health impacts for Inga. And unlike modern laparoscopic surgery, with its tiny incisions and short hospital stays, the surgery to remove the Inga’s kidney involved a large incision that cut through abdominal muscles and required a long recovery.

While these advancements in medicine were interesting, I found my conversation with Bill Goodnight (Inga’s son and Gary’s brother) about his memories from this time equally informative. In many ways their attitudes towards Gary’s condition and treatment seemed quite modern.

Gary Goodnight was aware that his kidneys weren’t going to last and actively followed the news about the emerging field of transplants. Both Bill and his mother had themselves tested to see which might make a good match. And, similar to today’s patients and families with life threatening conditions, the Goodnight family approached the procedure with hope.

Kim Smuga-Otto is a student in UC Santa Cruz’s science communication program and a writing intern in the medical school’s Office of Communication and Public Affairs.

One size seldom fits all, so it’s not surprising that one treatment regimen may not suit all patients with the same condition. Now, a new study of end-stage kidney failure shows the importance of taking factors like cause and circumstances of a patient’s disease into account when designing a treatment plan.

The study (subscription required) began when Stanford nephrology fellow Michelle O’Shaughnessy, MD, noted that patients with end-stage kidney-failure usually received the same generic treatment plan (dialysis or a kidney transplant), even though there are different causes of the disease and a patient’s condition can progress to kidney failure via many different routes.

[E]ach of the many glomerular disease subtypes is unique. In certain subtypes, the immune system attacks the kidneys; in others, it damages the blood vessels.

As a result, the various subtypes are treated using different methods before the kidneys begin to fail. The treatments may include steroids or stronger immunosuppressant medications. The resulting side effects can range from severe infections to diabetes to cancer.

For their work, O’Shaughnessy and her colleagues examined data collected from 84,301 patients with end-stage kidney disease caused by one of six major subtypes of glomerular disease. The results showed that the type of glomerular disease significantly affected how long the patient lived after they developed kidney failure; mortality ranged from 4 percent per year for one type of patient to 16 percent per year for another.

“It’s important to know why one kidney patient does well and another does poorly,” concluded O’Shaughnessy. “If physicians take into consideration what caused the kidneys to fail in the first place and what types of treatments patients received prior to kidney failure, it could possibly improve the patients’ quality of life or increase their life span.”

Skin is superficial, literally. But it’s also really deep, as I realized while editing the just-published issue of Stanford Medicine magazine. The summer issue features the special report “Skin deep: The science of the body’s surface.”

I learned from the chair of Stanford’s Department of Dermatology, Paul Khavari, MD, PhD, that thousands of diseases affect the skin. And I learned it’s surprisingly abundant: An average-sized adult is covered with about 20 square feet of skin.

Research on skin is thriving, in part, because skin is so easy to get hold of, Khavari told me. “The accessibility of skin tissue to the application of new technologies, including genomics, proteomics, and metabolomics, make this a watershed moment for progress in alleviating the tremendous suffering caused by the global burden of skin disease,” he said.

The magazine, produced with support from the dermatology department, includes articles not only about new treatments, but also insights into how skin works when it’s healthy and how to keep it that way. In a Q&A and audio interview, actress and playwright Anna Deavere Smith, who is African-American, addresses skin’s social meaning, discussing her relationship to her own skin and how, as a writer and actor, she gets under the skin of her characters. The online version of the magazine includes audio of an interview with Smith.

Also in the issue:

“The butterfly effect“: A story about two young men coping with one of the world’s most painful diseases — the skin-blistering condition epidermolysis bullosa — including news about an experimental treatment to replace their broken genes. The online version includes a video with a patient at home and interviews with experts on the condition.

“Surviving melanoma“: A report on progress being made after years of stagnation in treating the most deadly skin cancer: melanoma.

“The rarest of rashes“: A look at one of Stanford Medicine’s great accomplishments in dermatology: successful treatment of a rare but dangerous rash — cutaneous lymphoma, a form of blood cancer that spreads to the skin.

“Wither youth“: A feature on research seeking to answer the question: Why does skin age?

“New lungs, new life“: The story of a young woman who lost her smile and had it restored through surgery.

The issue also includes a story considering the rise in number of castoff donor hearts, despite a shortage of the organs for transplants, and an excerpt from Jonas Salk: A Life, a new biography of the polio-vaccine pioneer, written by retired Stanford professor Charlotte Jacobs, MD.

Researchers in the U.K. have found a way to make growing synthetic tissue more sustainable. At present, the size of engineered tissues is limited because the cells die from lack of oxygen when the pieces get too big. By adding an oxygen-carrying protein to the stem cells prior to combining them with tissue scaffolding, the researchers overcame this problem.

We were surprised and delighted to discover that we could deliver the necessary quantity [of oxygen] to the cells to supplement their oxygen requirements. It’s like supplying each cell with its own scuba tank, which it can use to breathe from when there is not enough oxygen in the local environment.

Hollander also comments on the significance of the research:

We have already shown that stem cells can help create parts of the body that can be successfully transplanted into patients, but we have now found a way of making their success even better. Growing large organs remains a huge challenge but with this technology we have overcome one of the major hurdles.

Creating larger pieces of cartilage gives us a possible way of repairing some of the worst damage to human joint tissue, such as the debilitating changes seen in hip or knee osteoarthritis or the severe injuries caused by major trauma, for example in road traffic accidents or war injuries.

When 17-year-old TJ Balliao was diagnosed with heart failure earlier this year, his doctors at Lucile Packard Children’s Hospital Stanford told him that he needed to receive a ventricular assist device right away. TJ was experiencing bouts of unstable heart rhythm so serious that medication alone wasn’t enough to keep him alive. The VAD, a pump implanted in his heart to help it move blood through his body, could help him survive long enough to receive a heart transplant.

But something unexpected happened after the surgery to implant TJ’s ventricular assist device. He made a strong recovery – so strong that his cardiologist, David Rosenthal, MD, offered him the opportunity to go home with his VAD, graduate from high school with his class this June, and delay a heart transplant indefinitely.

In a recent story I wrote about TJ’s case, Rosenthal explained how this could benefit TJ not just now, but also in the long run:

“It’s possible that using a VAD to intentionally delay a heart transplant could add to the patient’s total lifespan,” said Rosenthal, who directs the hospital’s pediatric heart failure and transplantation program and is professor of pediatrics at the Stanford University School of Medicine. “Survival after transplant is not as long as the natural lifespan, especially for children.”

The benefits of a VAD are many. It helps patients maintain strength while waiting for a new heart; otherwise, heart failure weakens the body, making recovery from eventual transplant more difficult. When a child is stabilized by use of a VAD, the medical team can be more selective about choosing a donor heart that is an excellent match for the recipient, too. “Plus,” said Rosenthal, “there is some likelihood that a small proportion of patients’ hearts will be able to recover and those children will avoid transplant completely.”

TJ and his medical team aren’t sure if or when he will ultimately move toward getting a heart transplant. But he’s been accepted to San Jose State University to study civil engineering, so he may be in class in the fall with his VAD battery pack at his side.

These days, Carlos Esquivel, MD, PhD, is best known as one of the top pediatric liver transplant surgeons. But just a few decades ago, he worked as a generalist physician in an ill-equipped Costa Rican village located across from a river teeming with man-sized crocodiles.

Esquivel told a gripping tale of his journey from his native Costa Rica to Stanford during a recent Café Scientifque presentation. He described how he spent only a year in remote San Vito before traveling to the United States and joining the lab of innovative surgeon F.W. Blaisdell, MD, who took Esquivel under his wing and treated him like a son. On to Sweden, where Esquivel earned his post-doctorate degree, before mastering his transplantation skills with Thomas Starzl, MD, PhD, who is known as the “father of trasnplantation” and conducted the first human liver transplant in 1963.

Back then, transplant surgeons wore knee-high fishing waders to perform transplantations — they were that messy, Esquivel said. And few dared to do liver transplants in children. Fast-forward to today: Transplant surgeries are shorter, much less bloody, and much more survivable thanks to the improvements in technology and immunosuppressant drugs. Last year, the team at Lucile Packard Children’s Hospital Stanford tallied a 100 percent one-year survival rate, Esquivel told the audience.

Now, the primary problem is the shortage of organs. More than 120,000 people in the United States are waiting for a new organ. Kidneys are most in-demand, but thousands of people are also waiting for new livers. And like kidneys, livers can be taken from living donors, Esquivel said. Sometimes, an adult liver can even be split in two, saving the lives of another adult and a child.

Livers can regenerate, making it an ideal organ to donate. However, the donation surgery can cause complications and donation is a choice that potential donors — and their doctors — should consider carefully, Esquivel said.

Esquivel said surgeries are physically taxing, but also take a great deal of mental preparation. Before surgeries, he said he runs through all the scenarios, trying to prepare for every possibility.

To raise awareness about organ donation, Esquivel, an avid cyclist, completed an across-the-county bicycle race with a former transplant patient. And he has high hopes for the future. Once, transplanted livers only lasted 12 to 15 years, but today, some livers last as long as 30 years, Esquivel said.

As a health writer, I’ve interviewed and written about numerous heart patients whose lives were saved when someone else died and donated their hearts for transplantation.

Those patients expressed both the anguish of hoping and praying for a new heart — when that means someone else has to die — and the overwhelming gratefulness for those donor hearts that saved their lives.

So when I wrote a story about a new Stanford study that shows an increasing number of donor hearts being rejected for transplantation, it struck a chord.

The study, published today online in the American Journal of Transplantation, found that the number of hearts rejected for transplant by surgeons and transplant centers is on the rise despite the growing need for such organs. As cardiologist Kiran Khush, MD, the lead author of the study, said in my story on the work, “We’ve become more conservative over the past 15-20 years in terms of acceptance, which is particularly troubling because of the national shortage of donor hearts and the growing number of critically ill patients awaiting heart transplantation.”

Khush and her colleagues sought to study national trends in donor-heart use by examining data from the federal government’s Organ Procurement and Transplantation Network on all donated hearts from 1995-2010. Of 82,053 potential donor hearts, 34 percent were accepted and 48 percent were declined. The remainder were used for other purposes such as research.

The researchers found a significant decrease in donor heart acceptance, from 44 percent in 1995 to 29 percent in 2006, which rebounded slightly to 32 percent in 2010. They also found, as I wrote in the story:

Among a portion of donor hearts that are referred to as “marginal” — those with undesirable qualities, such as being small or coming from an older donor — their use in transplantation varied significantly across geographical regions depending on choices made by the surgeons and the transplant centers.

The study explored possible reasons for so few organs being accepted. Increasing scrutiny by regulatory agencies of the 140 or so transplant centers across the country may have had the unintended result of making surgeons and centers more risk averse and as a result reject more hearts. Also, an increasing us of mechanical circulatory support devices that help keep patients alive while waiting for donor hears, may cause surgeons to wait longer for “better hearts.”

Imagine learning you have an illness. It’s the same illness that killed your mother. You watched her fade, the last years of her life dreadful to watch, unimaginably tough to endure. The same fate awaits you. Until… it doesn’t. Now there’s a therapy that just might save you.

That’s the story of San Francisco Bay Area resident Cynthia Alcaraz-Jew, featured in the fall issue of Stanford Medicine Magazine. Now in her late 40s, Alcaraz-Jew, like her mother, suffers from a rare genetic condition called Alport Syndrome. The ailment leads to kidney, ear and eye problems.

Alcaraz-Jew didn’t immediately luck out. Her kidneys failed first and her younger brother, Xavier, a perfect immunologic match, offered to donate his kidney. Great news, of course, but a transplant usually means years of immunosuppressive drugs, which leave bones brittle and can lead to infections, heart disease, or even, ironically kidney failure.

Thanks to her perfectly matched kidney, Alcaraz-Jew was able to enroll in a trial led by Stanford immunologist Samuel Strober, MD, that aims to wean transplant patients off immunosuppressive drugs. From the article:

Of the 24 kidney transplant patients with perfectly matched donors who enrolled in the trial beginning in 2000, 16, including Alcaraz-Jew, are living drug free, and three others are working to get off the medications, Strober says. The team is planning to publish a paper summarizing the research results in the near future.

And the photo? That’s Alcaraz-Jew and her husband swimming with whale sharks in Mexico earlier this year.